The overall objective of our Phase I and Phase II research and development effort is to achieve unprecedented preservation of monoclonal antibodies as diagnostics and therapeutics for human use. In Phase I we want to explore the utility of our recently discovered method of controllably dehydrating proteins as amorphous microspheres, applying it specifically to monoclonal antibodies. We want to determine how and to what extent this new procedure maintains an antibody in its native functional form. The overall technical question we will attempt to answer in order to determine the Phase I feasibility of the proposed approach is: Can controlled dehydration of antibody solution-based emulsions ensure molecular stability of an antibody preparation, and preserve it in storage, transport, and use? The importance of this question with respect to antibody preservation is that the current preservation paradigm for many biologics is either refrigeration or a lyophilization process that can nevertheless damage protein structure and compromise its function. Many antibodies appear not to be lyophilizable and only have a recommended shelf life in aqueous liquid at 4oC on a few months time scale. Experimentally, to address these problems we bring a new and unique perspective to the process of antibody preparation by using a micropipette manipulation platform. This technique allows us to controllably dehydrate single microdroplets as emulsions in water-dissolving media forming a glassified microsphere that is not completely dehydrated. We can then observe the rehydration of the microsphere in an aqueous solution. [unreadable] The scientific basis for this enabling technology comes from a significant amount of preliminary data already carried out on several protein model systems at Duke University with David Needham (consultant on this project). This SBIR proposal came about when a large medical device and pharmaceutics company, Becton Dickinson (a possible future pipeline to commercialization), became very interested in our emerging new experimentation and theory in microdroplet, microsphere, and nanosphere technologies for antibodies. This SBIR application is well placed to move towards the goal of commercialization of the technology. [unreadable] This SBIR will focus exclusively on a major class of proteins, monoclonal antibodies, and the huge commercial interest that is invested in their preservation and stability. The underlying scientific innovation for this SBIR is in single particle and nanodispersion studies for controlled protein dehydration, specifically as it applies to creating stabilized antibody microspheres that avoid damage due to lyophilization yet are still in a sufficiently dehydrated state that they preserve antibody structure and function.This SBIR then seeks to use a micropipette platform to establish to what extent the dehydration procedures we are developing can in fact provide unprecedented preservation and stability for diagnostic and therapeutic monoclonal antibodies. PUBLIC HEALTH RELEVANCE: The overall objective of our Phase I and Phase II research and development effort is to achieve unprecedented preservation of monoclonal antibodies as diagnostics and therapeutics for human use. In Phase I, we will explore the utility of our recently discovered method of controllably dehydrating proteins as amorphous microspheres, applying it specifically to the preservation study for monoclonal antibodies. [unreadable]